Blanco Jorge C G, Pletneva Lioubov M, Otoa Raymonde O, Patel Mira C, Vogel Stefanie N, Boukhvalova Marina S
Sigmovir Biosystems Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, United States.
Sigmovir Biosystems Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, United States.
Vaccine. 2017 Jul 13;35(32):3951-3958. doi: 10.1016/j.vaccine.2017.06.009. Epub 2017 Jun 16.
Maternal immunization directed to control RSV infection in newborns and infants is an appealing vaccination strategy currently under development. In this work we have modeled maternal vaccination against RSV in cotton rats (CR) to answer two fundamental questions on maternal vaccine safety. We tested (i), whether a known, unsafe RSV vaccine (i.e., FI-RSV Lot 100 vaccine) induces vaccine enhanced disease in the presence of passively transferred, RSV maternal immunity, and (ii) whether the same FI-RSV vaccine could induce vaccine enhanced disease in CR litters when used to immunize their RSV-primed mothers. Our data show that FI-RSV immunization of pups with subsequent RSV infection results in vaccine-enhanced disease independent of whether the pups were born to RSV-seropositive or RSV-seronegative mothers, and that FI-RSV immunization of RSV-seropositive mothers does not present a health risk to either the mother or the infant. Our study also raises a novel concern regarding infant immunization, namely that "safe" RSV vaccines (e.g., live RSV administered intramuscularly) may induce vaccine-enhanced disease in RSV-infected pups born to seropositive mothers. Finally, we describe for the first time a sharp decrease in RSV neutralizing antibody titers in immunized seropositive CR at the time of delivery. This decline may reflect maternal immune suppression, potentially pinpointing a window of increased vulnerability to RSV infection that could be alleviated by effective immunization of expectant mothers.
旨在控制新生儿和婴儿呼吸道合胞病毒（RSV）感染的母体免疫是目前正在研发的一种有吸引力的疫苗接种策略。在这项研究中，我们在棉鼠（CR）中对RSV母体疫苗接种进行了建模，以回答关于母体疫苗安全性的两个基本问题。我们测试了：（i）一种已知的不安全RSV疫苗（即FI-RSV批次100疫苗）在存在被动转移的RSV母体免疫的情况下是否会诱发疫苗增强疾病；以及（ii）当使用相同的FI-RSV疫苗免疫其已接触过RSV的母亲时，是否会在CR幼崽中诱发疫苗增强疾病。我们的数据表明，用FI-RSV免疫幼崽并随后感染RSV会导致疫苗增强疾病，无论幼崽是由RSV血清阳性还是血清阴性的母亲所生，并且用FI-RSV免疫血清阳性的母亲对母亲或婴儿均无健康风险。我们的研究还引发了关于婴儿免疫的一个新问题，即“安全”的RSV疫苗（例如肌肉注射的活RSV疫苗）可能会在血清阳性母亲所生的RSV感染幼崽中诱发疫苗增强疾病。最后，我们首次描述了免疫血清阳性的CR在分娩时RSV中和抗体滴度急剧下降。这种下降可能反映了母体免疫抑制，潜在地指出了一个对RSV感染易感性增加的窗口期，这可以通过对孕妇进行有效免疫来缓解。
